title: Activation-induced deaminase-coupled DNA demethylation is not crucial for the generation of induced pluripotent stem cells.
abstract: DNA methylation constitutes a major obstacle in the reprogramming of cells to pluripotency. Although little is known regarding the molecular mechanisms of DNA demethylation, activation-induced deaminase (AID), which is known to function in antibody diversification, has been implicated in DNA demethylation through a base excision repair (BER)-mediated pathway. Here we comprehensively examine the plausibility of coupled AID-BER demethylation in the generation of induced pluripotent stem cells (iPSCs) and show that AID is dispensable for reprogramming cells into iPSCs. Additionally, the overexpression of AID and other factors involved in AID-coupled DNA demethylation does not increase the efficiency of reprogramming. Moreover, BER is not likely to play a role in this process. Our results indicate that the reactivation of key genes governing the pluripotency circuitry occurs through a mechanism that is independent of deamination-coupled demethylation.
authors.affiliation: 1 School of Medicine, Konkuk University , Seoul, South Korea .
authors.forename: Omer
authors.initials: O
authors.lastname: Habib
authors.forename: Gizem
authors.initials: G
authors.lastname: Habib
authors.forename: Jeong Tae
authors.initials: JT
authors.lastname: Do
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Chung
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D065150:Cellular Reprogramming / Q000235:genetics*; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004260:DNA Repair / Q000235:genetics; D004622:Embryo, Mammalian; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005822:Genetic Vectors; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; C513672:Zfp42 protein, mouse; D014157:Transcription Factors; D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase